The objectives of this proposal are: 1) Investigate in vitro and in vivo mechanisms of adaptation of FeSV to heterospecies, i.e., cat to sheep. We have been successful in producing sarcomas in neonatal sheep with FeSV but only by first adapting the virus to sheep cells replicating FeSV as source of inoculum. We wish to elucidate some of the viral mechanisms of this phenomenon. 2) To determine immunologic responses of host to its tumor in large outbred animals. We have already conducted preliminary experiments whereby we can cannulate regional lymphatics draining stimulated lymph and lymphatics draining distant nodes. Lymphatic cannulation is impossible in small laboratory animals and for various reasons impractical in medium or large sized outbred animals in which tumors can be induced which makes this sheep model unique. Thereby, this outbred animal tumor model provides for the opportunity to collect peripheral blood, lymphoid cells, blood and lymph plasma in large quantities for in vitro studies; whereby a series of definitive immunologic experiments can be performed on the same individual. These studies will provide information concerning the immunologic responses of progressive and regressive tumors and factors responsible for dissemination of neoplastic growths. 3) To use information gained from objectives 1) and 2) above to develop new approaches of immunotherapy combined with surgery, radiotherapy and chemotherapy. We will be able to investigate the role of autochthonous, allogeneic and xenogeneic approaches combined with conventional therapys in induced sarcomas of sheep and induced and spontaneous tumors of feline sarcoma complex.